加巴喷丁杂质E | 67950-95-2

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 加巴喷丁杂质E
• 中文别名: 1-羧基环己烷乙酸；加巴喷丁相关化合物E
• 英文名称: 1-carboxycyclohexylacetic acid
• 英文别名: cyclohexane-1-carboxy-1-acetic acid；1-carboxy-1-cyclohexane acetic acid；1-(carboxymethyl) cyclohexanecarboxylic acid；1-Carboxycyclohexaneacetic Acid；1-(carboxymethyl)cyclohexane-1-carboxylic acid
• CAS: 67950-95-2
• 化学式: C₉H₁₄O₄
• 分子量: 186.208
• InChiKey: SDAXMMUAZRUWNL-UHFFFAOYSA-N

物化性质

• 熔点：
  130-132?C
• 沸点：
  390.3±15.0 °C(Predicted)
• 密度：
  1.246
• 溶解度：
  氯仿（微溶）、DMSO（微溶）、甲醇（微溶）、水（微溶)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2917209090
• WGK Germany：
  3
• 储存条件：
  -20°C，密封保存，并保持干燥。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 1-(Carboxymethyl)cyclohexane-1-carboxylic acid
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 1-(Carboxymethyl)cyclohexane-1-carboxylic acid
CAS number: 67950-95-2

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C9H14O4
Molecular weight: 186.2

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  加巴喷丁杂质E 在 乙酰氯 作用下， 反应 3.0h， 以94%的产率得到2-噁螺[4.5]癸烷-1,3-二酮
  参考文献：
  名称：

  高Fsp3特征的螺[环烷-吡啶并酮]的合成

  摘要：

  背景：如今，在药物设计和发现过程中，除其候选药物的生物活性外，还非常关注候选药物的理化参数。不利的理化参数会阻碍候选药物的成功。 目标：Lovering等。介绍了Fsp3特性作为碳键饱和度的量度，该特性与药物的理化副弹药有关。药物研究集中于合成具有高Fsp3特性的化合物。 方法：为了改善候选药物分子的物理化学性质（clogP，溶解度，更有利的ADME谱等），一种可能性是用生物等排杂芳族部分（例如用一个或两个含氮原子的系统）代替全碳芳族系统例如吡啶和哒嗪等。另一种选择是增加候选药物的Fsp3特性。设计新的螺环化合物时考虑了这两个方面，在本研究中描述了其合成方法。 结果：从2-氧杂螺[4.5]癸烷-1,3-二酮或2-氧杂螺[4.4]壬烷-1,3-二酮开始，通过与苯甲醚或四氢呋喃的Friedel-Crafts反应获得了相应的酮羧酸。用肼，甲基肼或苯肼处理酮羧酸，形成哒嗪酮环。哒嗪酮的N-烷基化反

  DOI：

  10.2174/1570180816666190710130119
• 作为产物：
  描述：

  加巴喷丁 在 盐酸 、 ruthenium trichloride 、 sodium perchlorate 、 sodium hydroxide 、 potassium hexacyanoferrate(III) 作用下， 以 水 为溶剂， 反应 6.0h， 生成 加巴喷丁杂质E
  参考文献：
  名称：

  在催化量 Ru(III) 存在下室温下碱性六氰基铁酸盐 (III) 氧化加巴喷丁的机理研究

  摘要：

  摘要 用分光光度法研究了在碱性水溶液中以恒定离子强度为 0.5 mol dm -3 的六氰基铁酸盐 (III) 氧化加巴喷丁的动力学。该反应在 [HCF(III)] 中是一级反应，在 [碱] 中是低于单元级的。反应速率与[加巴喷丁]无关。研究了反应介质的添加产物、离子强度和介电常数的影响。鉴定出加巴喷丁的氧化产物。已经提出了合适的机制。计算了不同机理步骤中涉及的反应常数。计算并讨论了该机构的激活参数。

  DOI：

  10.1016/j.molstruc.2008.05.006

文献信息

• [EN] FURO[3,2-B]PYRIDINE COMPOUNDS USEFUL AS INHIBITORS OF THE PAR-2 SIGNALING PATHWAY<br/>[FR] COMPOSÉS FURO[3,2-B]PYRIDINE UTILES EN TANT QU'INHIBITEURS DE LA VOIE DE SIGNALISATION PAR-2
  申请人：VERTEX PHARMA

  公开号：WO2018057588A1

  公开（公告）日：2018-03-29

  Disclosed are chemical entities which are compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, R1, R2, E, n and Z are as defined herein. These chemical entities are useful as inhibitors of the PAR-2 signaling pathway. These chemical entities and pharmaceutically acceptable compositions comprising such chemical entities can be employed for treating various diseases, disorders, and conditions.

  公开了式(I)的化合物及其药用可接受的盐，其中A，R1，R2，E，n和Z定义如本文中。这些化学实体作为PAR-2信号通路的抑制剂是有用的。这些化学实体和包含这些化学实体的药用可接受组合物可用于治疗各种疾病、障碍和状况。
• Synthesis, Physicochemical and Anticonvulsant Properties of NewN-4-Arylpiperazin-1-yl Amides of (2-Aza-1,3-dioxospiro[4.4]non-2-yl)- and [4.5]dec-2-yl)-propionic Acid
  作者：Jolanta Obniska、Krzysztof Kaminski、Lukasz Hondo、Alfred Zejc

  DOI：10.1002/ardp.200700038

  日期：2007.8

  structurally related to the previously described N‐4‐arylpiperazin‐1‐yl amides of 2‐aza‐1,3‐dioxospiro[4.5]dec‐2‐yl‐acetic acid, were synthesized. The designed compounds 5–15 were prepared by condensation of the formerly obtained (2‐aza‐1,3‐dioxospiro[4.5]dec‐2‐yl)‐ (3) and (2‐aza‐1,3‐dioxo[4.4]non‐2‐yl)‐(4) propionic acids with the appropriately substituted 4‐arylpiperazines, in the presence of the

  继续寻找新的抗惊厥药，一系列N-4-芳基哌嗪-1-基2-氮杂-1,3-二氧螺[4.4]非-2-基-(5-8)和[4.5]dec- 2-基-(9-15)丙酰胺，在结构上与之前描述的2-氮杂-1,3-二氧螺[4.5] dec-2-基-乙酸的N-4-芳基哌嗪-1-基酰胺相关，是合成的。设计的化合物 5-15 是通过先前获得的 (2- aza - 1,3-dioxospiro [4.5] dec - 2-yl) - (3) 和 (2- aza - 1,3-dioxo [4.4] 的缩合制备的] 非 2-基) - (4) 丙酸与适当取代的 4-芳基哌嗪，在 N, N-羰基二咪唑 (CDIM) 试剂存在下。在最大电休克癫痫发作 (MES) 和皮下戊四唑 (scPTZ) 癫痫发作阈值测试中，测试了所有化合物的抗惊厥活性。几种化合物 7-10，
• Evaluation of Various N-Substituted Azaspiranedione Derivatives as Potential Antimicrobial Agents
  作者：K.R. Scott、Poledi G. Kennedy、Murray Kemp、Vasant G. Telang、H.W. Matthews

  DOI：10.1002/jps.2600720222

  日期：1983.2

  A series of N-substituted hydrazines were condensed with various spiro[4.5] and [5.5] anhydrides and the resultant N-substituted azaspiranediones were evaluated for antimicrobial activity. None displayed any significant activity in a variety of organisms tested.

  将一系列的N-取代的肼与各种螺[4.5]和[5.5]酸酐缩合，并评估所得的N-取代的氮杂氮杂双阴离子的抗菌活性。在测试的各种生物中，没有一个显示出明显的活性。
• Spiro[4.5] and spiro[4.6] carboxylic acids: cyclic analogs of valproic acid synthesis and anticonvulsant evaluation
  作者：K. R. Scott、Jacqueline A. Moore、Theodore B. Zalucky、Jesse M. Nicholson、Jo Ann M. Lee、Christine N. Hinko

  DOI：10.1021/jm00382a004

  日期：1985.4

  Spiro[4.5]decane-2-carboxylic acid (12a), spiro[4.5]decane-2,2-dicarboxylic acid (11a), spiro[4.6]undecane-2-carboxylic acid (12b), spiro[4.6]undecane- 2,2-dicarboxylic acid (11b), and spiro[4.6]undecane-2-acetic acid (13) were synthesized by an improved method and evaluated for anticonvulsant activity. These analogues were synthesized to evaluate the role of the carboxylic acid group as an essential substituent

  螺[4.5]癸烷-2-羧酸（12a），螺[4.5]癸烷-2,2-二羧酸（11a），螺[4.6]十一烷-2-羧酸（12b），螺[4.6]十一烷-通过改进的方法合成了2,2-二羧酸（11b）和螺[4.6]十一烷-2-乙酸（13），并评估了其抗惊厥活性。合成这些类似物以评估羧酸基团在丙戊酸（二正丙基乙酸，1）中的作用。已知碳环螺烷可抵抗代谢改变，因此这些化合物引起的任何活性将归因于羧酸功能而不是由于任何代谢改变。螺[4.6]十一烷-2-羧酸（12b）是测试过的最活跃的类似物，对12b的戊四氮和微毒素的评价优于1。12b未能提供足够的保护作用，以防止小鼠遭受最大的电击惊厥，双瓜氨酸或士的宁。讨论了导致这些结果的可能原因。
• Synthesis and anticonvulsant activity of new fluorinated N-phenyl- and N-benzyl-2-azaspiro[4.4]nonane- and [4.5]decane-1,3-dione derivatives: Part III
  作者：Jolanta Obniska、Krzysztof Kaminski、Agnieszka Zagorska、Agnieszka Dzierzawska-Majewska、Janina Karolak-Wojciechowska

  DOI：10.1016/j.jfluchem.2006.01.009

  日期：2006.3

  A series of N-phenyl- and N-benzyl-2-azaspiro[4.4]nonane- and [4.5]decane-1,3-diones containing a fluoro or trifluoromethyl substituents at the aryl ring was synthesized and tested for their anticonvulsant activity in the maximal electroshock (MES) and subcutaneous metrazole (sc.Met) tests. Among them, the most active were N-benzyl derivatives with fluoro and trifluoromethyl substituents especially

  合成了一系列在芳基环上含有氟或三氟甲基取代基的N-苯基-和N-苄基-2-氮杂螺[4.4]壬烷-和[4.5]癸烷-1,3-二酮，并测试了它们的抗惊厥活性。最大电击（MES）和皮下甲拉唑（sc.Met）测试。其中，最活跃的是N具有氟和三氟甲基取代基的-苄基衍生物，特别是在芳基部分的2位上。在酰亚胺氮原子上引入苯环会导致活性较低的化合物。获得的结果表明，与相应的氯，甲氧基或甲基类似物相比，氟或三氟甲基取代基的掺入提高了抗惊厥活性。晶体学上获得的一种活性和两种非活性衍生物在苯环的2位或-3位具有三氟甲基取代基的构象最初用于分子静电势（MEP）计算。对于活性和非活性分子，羰基氧原子上的MEP分布是不同的。